FELDENE FAST - PACKAGE LEAFLET - LEAFLETS

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Feldene Fast - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Piroxicam

FELDENE FAST 20 mg sublingual tablets

Why is Feldene Fast used? What is it for?

Before prescribing Feldene Fast, your doctor will evaluate the benefits of this medicine against the risk of side effects. Your doctor may need to review you periodically and will tell you how often you will need to be checked during treatment with Feldene Fast.

Feldene is an anti-inflammatory and pain reliever medicine which is used to relieve some symptoms caused by osteoarthritis (osteoarthritis: degenerative joint disease), rheumatoid arthritis and ankylosing spondylitis (rheumatism of the spine), such as swelling, stiffness and pain in the joints. Feldene Fast does not cure arthritis and will only relieve you as long as you continue to take it.

Your doctor will only prescribe Feldene Fast when other non-steroidal anti-inflammatory medicines (NSAIDs) are no longer helpful in relieving your symptoms.

Contraindications When Feldene Fast should not be used

DO NOT TAKE FELDENE FAST

If you are allergic to the active substance or any of the other ingredients of this medicine
If you have ever had an ulcer or bleeding or perforation in the stomach or intestines.
If you have an ulcer or bleeding or perforation in the stomach or intestines.
If you have or have had previous gastrointestinal disorders (inflammation of the stomach or intestines) which predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancer, diverticulitis (inflamed or infected pockets / cavities in the colon).
If you are taking other NSAIDs, including selective COX-2 inhibitors and acetylsalicylic acid (found in many medicines used to relieve pain and lower fever). Remember that many NSAIDs are also available without a prescription.
If you are taking blood thinners, such as warfarin, to prevent blood clots.
If you have ever had a severe allergic reaction to piroxicam, other NSAIDs and other medicines, especially severe skin reactions (regardless of their severity), such as erythema multiforme, exfoliative dermatitis (intense redness of the skin, with flaky or layered peeling ), vesiculo-bullous reactions: Stevens-Johnson syndrome, characterized by red, corroded, bloody, or crusted skin with blisters, and necrotic epidermolysis, characterized by blistering and peeling of the surface layer of the skin.
If you have had symptoms of asthma, rhinitis, nasal polyposis, angioedema or urticaria during treatment with acetylsalicylic acid or other NSAIDs.
If you are pregnant or think you are.
If you are breastfeeding.
If you are under the age of 18.
If you have severe liver disease.
If you have severe kidney disease.
If you have moderate or severe heart failure.
If you have severe hypertension.
If you have severe blood disorders.
If you have a bleeding diathesis (a predisposition to bleed frequently).

If any of these conditions exist, Feldene Fast should not be prescribed for you. Tell your doctor immediately.

Precautions for use What you need to know before taking Feldene Fast

Talk to your doctor or pharmacist before taking Feldene Fast.

Take special care with Feldene Fast and always tell your doctor before using Feldene Fast; like all non-steroidal anti-inflammatory drugs, Feldene Fast can cause severe stomach and bowel reactions such as pain, bleeding and ulcer.

You should stop taking Feldene Fast immediately and contact your doctor if you have stomach pain or if you have any signs of stomach or bowel bleeding, such as passing black or bloodstained stools or vomiting blood.

You should stop using Feldene Fast immediately and contact your doctor if you have an allergic reaction such as a rash, swollen face, wheezing or difficulty in breathing.

If you are over 70, your doctor may wish to minimize the duration of your treatment and visit you more often when you are being treated with Feldene Fast.

If you are over 70 or are taking other medicines such as corticosteroids or certain medicines to treat depression called selective serotonin reuptake inhibitors (SSRIs), or acetylsalicylic acid to prevent blood clots, your doctor may prescribe them. together with Feldene Fastun medicine to protect the stomach and intestines.

You should not take this medicine if you are over 80 years old.

If you have or have had any medical problems or any form of allergy or if you are not sure whether you can take Feldene Fast please tell your doctor before taking this medicine.

Tell your doctor if you are taking any other medicines, including medicines obtained without a prescription. Medicines such as Feldene Fast may be associated with an increased risk of heart attack ('myocardial infarction') or stroke. Any risk is more likely with high doses and prolonged treatments. Do not exceed the recommended dose or duration of treatment.

If you have heart problems, have a history of stroke or think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or smoke) you should discuss your treatment with your doctor or pharmacist.

Feldene Fast, like other non-steroidal anti-inflammatory drugs, decreases platelet aggregation and lengthens clotting time; this eventuality should be remembered when carrying out haematological tests and requires vigilance when being treated simultaneously with drugs that inhibit platelet aggregation.

In vitro studies have shown that Feldene Fast interferes with the antiplatelet effect of low-dose aspirin and therefore may interfere with aspirin given as a prophylaxis of cardiovascular disease.

The concomitant use of NSAIDs, including Feldene Fast, with oral anticoagulants increases the risk of gastrointestinal and non-gastrointestinal bleeding, and should therefore be avoided. Oral anticoagulants include warfarin / coumarin-type anticoagulants and latest generation oral anticoagulants (eg . apixaban, dabigatran, rivaroxaban) If you are taking warfarin or other coumarin-type anticoagulants (see sections Contraindications and Other medicines and Feldene Fast) your doctor will monitor your clotting (INR)

Caution should be exercised if you have a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.

Particular caution is required if you have cardiovascular insufficiency, arterial hypertension, reduced hepatic or renal function, renal hypoperfusion, current or previous blood changes, and if you are on diuretic therapy.

If you are asthmatic, due to the interaction of the drug with the metabolism of arachidonic acid, crises of bronchospasm and possibly shock and other allergic phenomena may arise.

Since ocular alterations have been detected during NSAID therapy, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks.

As with other substances with similar action, increases in azotemia (levels of nitrogen in the blood) have been observed which do not progress beyond a certain level with continued administration and return to normal values once therapy is discontinued.

If you are diabetic it is advisable to have frequent blood tests.

Feldene Fast can cause fatal hepatitis and jaundice. Although these reactions are rare, Feldene Fast should be discontinued if liver function tests remain abnormal or worsen, if clinical signs and symptoms consistent with liver disease appear or if systemic manifestations occur (for e.g. eosinophilia, rash etc.).

Life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of Feldene, these initially appear as round red spots or circular patches often accompanied by blisters in the central part of the trunk.

Additional signs to note include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes).

These life-threatening rashes are often accompanied by flu-like symptoms. The rash may progress to the development of widespread blistering or peeling of the skin

The highest risk of severe skin reactions occurs within the first few weeks of treatment. If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis, with the use of Feldene Fast, Feldene Fast must no longer be used.

If you develop a skin rash or these skin symptoms, stop taking Feldene Fast, consult a doctor urgently and inform him that you are taking this drug.

If you are a patient with genetic polymorphisms (such as CYP2C9 * 2 and CYP2C9 * 3 polymorphisms) piroxicam should be administered with caution as the elimination of piroxicam from the body may be reduced and may have high levels of piroxicam in the blood.

If you are planning to become pregnant, have fertility problems or are investigating fertility, you should discuss your therapy with your doctor.

Interactions Which drugs or foods can modify the effect of Feldene Fast

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Medicines can sometimes interfere with each other. Your doctor may restrict the use of Feldene or other medicines, or you may need to take a different medicine. It is particularly important to report the following cases:

if you are taking aspirin or other non-steroidal anti-inflammatory medicines to relieve pain
if you are taking corticosteroids, medicines used to treat a variety of conditions such as allergies and hormone imbalances
if you are taking blood thinners such as warfarin to prevent blood clots
if you are taking certain medicines for depression called selective serotonin reuptake inhibitors (SSRIs)
if you are taking any medicines, such as aspirin, to prevent blood clots
if you are taking diuretics, ACE inhibitors, angiotensin II antagonists and beta-blockers
used in cases of high blood pressure and heart disease
if you are taking lithium
used for the treatment of depression
if you are taking quinolone antibacterials, used to treat bacterial infections
if you use intrauterine devices
if you are taking methotrexate, a medicine used to treat acute leukemia, arthritis (rheumatoid, psoriatic, polyarticular juvenile rheumatoid), psoriasis.

If you have any of these conditions, tell your doctor immediately.

FELDENE FAST WITH ALCOHOL

It is advisable not to drink alcohol while taking Feldene Fast.

Warnings It is important to know that:

PREGNANCY, BREASTFEEDING AND FERTILITY

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

If you are pregnant or think you are: tell your doctor as Feldene Fast is contraindicated.
If you are breastfeeding: you should not take Feldene Fast. Ask your doctor for advice: you may need to stop breastfeeding.
Fertility: if you are planning a pregnancy, have fertility problems or are investigating fertility, please tell your doctor, as Feldene Fast may not be suitable for you.

The use of NSAIDs, such as Feldene Fast, can delay or prevent rupture of ovarian follicles, which can result in reversible infertility. In women with difficulty conceiving or undergoing investigation for infertility, discontinuation of NSAIDs, including Feldene, should be considered. Fast.

DRIVING VEHICLES AND USING MACHINERY

If you feel dizzy or unusually tired, take special care when driving or using machines.

Feldene fast contains aspartame, a source of phenylalanine. It can be harmful to you if you have phenylketonuria.

Dosage and method of use How to use Feldene Fast: Dosage

Always take this medicine exactly as your doctor or pharmacist has told you.

If in doubt, consult your doctor or pharmacist. Your doctor will check you regularly to make sure you are taking the optimal dose of Feldene Fast. Your doctor will adjust your treatment to the lowest dose that best controls your symptoms. Under no circumstances should you change your dose without first informing your doctor.

Adults and the elderly:

The maximum daily dose of Feldene Fast is 20 milligrams to be taken as a single daily dose. If you are over 70, your doctor may prescribe a lower daily dose and shorten the duration of treatment.

Your doctor may prescribe Feldene Fast together with another medicine to protect the stomach and intestines from possible side effects.

Do not increase the dose:

If you feel that the medicine is not very effective, always talk to your doctor.

Overdose What to do if you have taken too much Feldene Fast

If you forget to take Feldene Fast:

Take the medicine as soon as you remember. If it is almost time for your next dose, do not take the missed dose, but take the next dose at the correct time. Do not take a double dose.

If you take more Feldene Fast than you should:

Symptoms: The most indicative symptoms of overdose are headache, vomiting, drowsiness, dizziness and syncope.

In case of accidental overdose of Feldene Fast, notify your doctor immediately or go to the nearest hospital.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Side Effects What are the side effects of Feldene Fast

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Feldene immediately and contact your doctor:

if you develop blisters, redness or flaking
and allergic such as skin rash, swelling of the face, lips or tongue which may cause difficulty in breathing or wheezing
if the skin or whites of the eyes are yellow (jaundice)
if you have any signs of bleeding in your stomach or intestines, such as passing black or bloodstained stools or vomiting blood
skin rash (rash), an "ulceration in any part of the body (such as skin, mouth, eyes, lips, or tongue), or any other sign of a reaction

All side effects related to Feldene are listed below.

Most common effects

Digestive tract ulcers and gastrointestinal bleeding
Nausea, vomiting, diarrhea, flatulence, constipation, stomach acid, abdominal pain, ulcerative stomatitis, inflammatory bowel disease (colitis and Crohn's disease)
Swelling of the ankles, legs and feet (fluid retention)
Increased blood pressure
Heart failure (difficulty in breathing and fatigue)

Less common effects

Heart attack (myocardial infarction)
Stroke
Anorexia
Tiredness
Anemia
Blisters, redness or peeling of the skin (rash) or ulceration anywhere on the body (e.g. skin, mouth, eyes, lips or tongue), or any other signs of allergic reactions such as skin rash, swelling of the face, lips, tongue , wheezing
Yellow discoloration of the skin and eyes (jaundice)
Increase in normal liver function values
Pancreatitis
Acute kidney failure, blood in the urine, difficulty urinating
Increase in non-protein nitrogen in the blood (increased blood urea nitrogen)
Swelling of the ankles, legs and feet (fluid retention)
Increased blood pressure (hypertension)
Nosebleeds
Headache
Drowsiness
Deafness or ringing in the ear
Dizziness
Visual disturbances
Malaise
Changes in the blood and lymphatic system
Gastritis Rare effects
Appearance of bruises
Alteration of blood sugar values (hypo and hyperglycemia)
Sweating
Change in body weight
Insomnia
Depression
Swelling, blistering or peeling of the skin
Skin photosensitivity
Dry mouth
Erethism
Alterations in the functioning of the bladder
Shock
Alopecia
Nail growth alterations
Fatal hepatitis

Very rare effects

Life-threatening skin rashes (Stevens-Johnson syndrome, toxic epiedermal necrolysis)

Effects of unknown frequency (frequency cannot be estimated from the available data)

Reversible female infertility
Nephrotic syndrome
Glomerulonephritis
Interstitial nephritis
Kidney failure

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the outer carton and inner label. The expiry date refers to the last day of that month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Contents of the pack and other information

What Feldene Fast contains

The active ingredient is piroxicam. Each sublingual tablet of Feldene Fast contains 20 mg piroxicam
The other ingredients are: gelatin, mannitol, aspartame, anhydrous citric acid.

What Feldene Fast looks like and contents of the pack

FELDENE Fast 20 mg sublingual tablets - 5 tablets: Carton containing 1 opaque PVC / PVDC and aluminum blister.

FELDENE Fast 20 mg sublingual tablets - 20 tablets: Carton containing 2 opaque PVC / PVDC and aluminum blisters.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Feldene Fast can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

FELDENE FAST 20 MG SUBLINGUAL TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each fast dissolving sublingual tablet contains:

Active principle

Piroxicam 20 mg

Excipients with known effects: aspartame.

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM

Sublingual tablets

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Piroxicam is indicated for the symptomatic treatment of osteoarthritis, rheumatoid arthritis or ankylosing spondylitis.

Due to its safety profile piroxicam is not a first choice NSAID (see sections 4.2, 4.3 and 4.4).

The decision to prescribe piroxicam should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).

04.2 Posology and method of administration

Prescribing for piroxicam should be initiated by a physician experienced in the diagnosis and treatment of patients with inflammatory or degenerative rheumatic diseases.

The maximum recommended daily dose is 20 mg.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms. The benefit and tolerability of treatment should be reassessed within 14 days. If continued treatment is necessary. , the latter must be associated with frequent re-evaluation.

Since the use of piroxicam has been shown to be associated with an increased risk of complications affecting the gastrointestinal (GI) tract, the possible need for combined therapy with gastro-protective agents (eg misoprostol or proton pump inhibitors ) should be carefully considered, particularly in elderly patients.

Dosage and indications in children have not yet been established.

In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.

04.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients, listed in section 6.1.

• Previous history of gastrointestinal ulcer, bleeding or perforation.

• Previous gastrointestinal disorders that predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancer or diverticulitis.

• Patients with active peptic ulcer, gastrointestinal inflammatory disorders or gastrointestinal bleeding.

• Patients with gastritis, dyspepsia, severe liver and kidney disorders, moderate or severe heart failure, severe hypertension, severe blood disorders, bleeding diathesis

• Concomitant use of other NSAIDs, including selective COX-2 inhibitors and acetylsalicylic acid, administered at analgesic doses.

• Concomitant use of anticoagulants (see sections 4.4 and 4.5).

• History of severe drug allergic reactions of any kind, particularly skin reactions such as erythema multiforme, Stevens-Johnson syndrome, necrotic epidermolysis.

• Previous skin reactions (regardless of severity) to piroxicam, other NSAIDs and other medicines.

• Known or suspected pregnancy, during lactation and in children (see section 4.6).

• Due to the presence in the formulation of aspartame, the product is contraindicated in phenylketonuria.

There is a possibility of cross-sensitivity with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. Piroxicam should not be administered to patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs cause symptoms of asthma, rhinitis, nasal polyposis, angioedema, urticaria.

04.4 Special warnings and appropriate precautions for use

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.

The clinical benefit and tolerability of the treatment should be reassessed periodically and the treatment should be stopped immediately upon the appearance of the first signs of skin reactions or major gastrointestinal events.

Gastrointestinal (GI) Effects, Risk of gastrointestinal ulceration, bleeding and perforation

NSAIDs, including piroxicam, can cause serious gastrointestinal events including bleeding, ulceration and perforation of the stomach, small intestine or colon, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients being treated with NSAIDs.

Both short and long-term exposure to NSAIDs carries an increased risk of serious GI events. Evidence from observational studies suggests that piroxicam, compared to other NSAIDs, may be associated with an increased risk of severe gastrointestinal toxicity. .

Patients with significant risk factors for serious GI events should only be treated with piroxicam after careful consideration (see section 4.3 and the section below).

The possible need for combination therapy with gastro-protective agents (eg misoprostol or proton pump inhibitors) should be carefully considered (see section 4.2).

Serious Gastrointestinal Complications

Identification of subjects at risk

The risk of developing serious gastrointestinal complications increases with age. An age over 70 is associated with a higher risk of complications. Administration to patients over 80 years of age should be avoided.

Patients on concomitant treatment with oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs), anticoagulants such as warfarin or antiplatelet agents, such as low-dose acetylsalicylic acid, have an increased risk of serious gastrointestinal complications (see below and section 4.5 ). As with other NSAIDs, the use of piroxicam in combination with gastro-protective agents (eg misoprostol or proton pump inhibitors) should be considered in these at-risk patients.

Patients and physicians should pay attention to the signs and symptoms of gastrointestinal ulcer and / or bleeding during treatment with piroxicam. Patients should be asked to report any new or unusual abdominal symptoms that occur during treatment. If a gastrointestinal complication is suspected during the course of treatment, the use of piroxicam should be discontinued immediately and further clinical evaluation and alternative treatment considered.

Cardiovascular and cerebrovascular effects

Adequate monitoring and instruction are required in patients with a history of hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.

Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg, myocardial infarction or stroke). There are insufficient data to exclude a similar risk for piroxicam.

Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with piroxicam after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Piroxicam decreases the aggregating power of platelets and lengthens the clotting time. However, piroxicam may also interfere with the antiplatelet effect of low dose aspirin (see section 4.5). These characteristics must be considered when performing haematological tests and when a patient is being treated with other substances that inhibit platelet aggregation.

Patients in whom renal function is impaired should be periodically monitored as the inhibition of prostaglandin synthesis caused by piroxicam in these patients can lead to a severe decrease in renal perfusion which may lead to acute renal failure. In this regard, elderly patients and those on diuretic therapy are considered at risk.

Caution should also be taken when treating patients with impaired liver function. Also for these it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment.

For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.

Since ocular alterations have been detected during NSAID therapies, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks. It is also advisable to frequently check the glycemic rate in diabetic patients and the prothrombin time in subjects undergoing a concomitant anticoagulant treatment with dicumarol derivatives.

Hepatic effects

Piroxicam can cause fatal hepatitis and jaundice. Although these reactions are rare, piroxicam should be discontinued if liver function tests remain abnormal or worsen, if clinical signs and symptoms consistent with liver disease appear, or in case of systemic manifestations (eg . eosinophilia, rash, etc.).

Skin reactions

The following life-threatening skin reactions have been reported with the use of Feldene Fast: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Patients should be informed of the signs and symptoms and monitored closely for skin reactions. The highest risk of developing SJS and TEN occurs in the first few weeks of treatment.

If symptoms and signs of SJS and TEN occur (e.g. progressive skin rash often with blistering or mucosal lesions) treatment with Feldene Fast should be discontinued.

The best results in the management of SJS and TEN are obtained with an early diagnosis and immediate discontinuation of therapy with any suspect drug. Early discontinuation is associated with a better prognosis.

If the patient has developed SJS or TEN with the use of Feldene Fast, Feldene Fast should no longer be reused in this patient.

Poor metabolisers of CYP2C9 substrates

In patients who are known or suspected poor metabolisers of CYP2C9 based on previous history / experience with other substrates of CYP2C9, piroxicam should be administered with caution as they may have excessively elevated plasma levels due to decreased metabolic clearance (see section 5.2).

Use with oral anticoagulants

Concomitant use of NSAIDs, including piroxicam, with oral anticoagulants increases the risk of gastrointestinal and non-gastrointestinal bleeding, and should therefore be avoided. apixaban, dabigatran, rivaroxaban). In patients taking warfarin / coumarin-type anticoagulants (see sections 4.3 and 4.5), anticoagulation (INR) should be monitored.

The use of piroxicam, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant.

Piroxicam administration should be discontinued in women who have fertility problems or who are undergoing fertility investigations.

04.5 Interactions with other medicinal products and other forms of interaction

Acetylsalicylic acid or other NSAIDs : as with other NSAIDs, the use of piroxicam together with acetylsalicylic acid or other NSAIDs, including other formulations of piroxicam, should be avoided as the available data do not allow to demonstrate that these combinations produce a greater improvement than that obtained with piroxicam alone; furthermore, the possibility of adverse reactions is increased (see section 4.4.). Studies in humans have shown that concomitant use of piroxicam and acetylsalicylic acid reduces the plasma concentration of piroxicam by approximately 80% of the usual value.

Piroxicam interacts with acetylsalicylic acid, with other non-steroidal anti-inflammatory substances and with substances that inhibit platelet aggregation (see sections 4.3 and 4.4).

In vitro studies have shown that piroxicam interferes with the antiplatelet effect of low-dose aspirin and therefore may interfere with aspirin given as a prophylaxis of cardiovascular disease.

Corticosteroids : increased risk of gastrointestinal ulcer or bleeding (see section 4.4).

Anticoagulants : NSAIDs, including piroxicam, may potentiate the effects of anticoagulants, such as warfarin. Therefore, the use of piroxicam together with anticoagulants such as warfarin should be avoided (see sections 4.3 and 4.4).

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : increased risk of gastrointestinal bleeding (see section 4.4.).

Diuretics, ACE inhibitors, angiotensin II antagonists and beta-blockers: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs including ACE inhibitors, angiotensin II antagonists and beta-blockers.

In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function), co-administration of an ACE inhibitor or angiotensin II antagonist and / or diuretic with agents that inhibit the cycle system oxygenase can lead to further deterioration of renal function, including possible acute renal failure, usually reversible.

These interactions should be considered in patients taking piroxicam concomitantly with ACE inhibitors or angiotensin II antagonists and / or diuretics.

Therefore, the combination should be administered with caution, especially in elderly patients.

Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy.

In case of concomitant use of drugs containing potassium or diuretics that cause potassium retention there is an additional risk of an increase in the serum potassium concentration (hyperkalaemia).

Lithium : the simultaneous administration of lithium and NSAIDs causes an increase in plasma lithium levels.

Piroxicam binds a lot to proteins and is therefore likely to displace other protein-bound drugs. Doctors will need to monitor patients on piroxicam and high protein binding drugs for any dose adjustments. Following administration of cimetidine, the absorption of piroxicam shows a slight increase. This increase, however, has not been shown to be clinically significant.

Methotrexate : when methotrexate is administered together with NSAIDs, including piroxicam, the NSAID can reduce the elimination of methotrexate and cause an increase in plasma levels of the latter. Caution is advised, especially in patients taking high dose methotrexate.

Avoid alcohol intake.

Piroxicam may decrease the effectiveness of intrauterine devices.

The use of non-steroidal anti-inflammatory drugs at the same time as quinolone drugs is not recommended.

04.6 Pregnancy and lactation

Piroxicam is contraindicated during pregnancy, established or suspected, and breastfeeding.

Fertility

Based on the mechanism of action, the use of NSAIDs, including piroxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility. consider discontinuing NSAIDs, including piroxicam.

Pregnancy

Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.

Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.

In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose

the fetus to:

• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);

• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;

the mother and the newborn, at the end of pregnancy, to:

• possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;

• inhibition of uterine contractions resulting in delayed or prolonged labor.

04.7 Effects on ability to drive and use machines

Piroxicam can modify the state of vigilance in such a way as to compromise the driving of motor vehicles and the engagement in activities that require alertness.

04.8 Undesirable effects

Gastrointestinal : the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).

Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of piroxicam (see section 4.4).

Gastritis has been observed less frequently.

Edema, hypertension, reversible female infertility and heart failure have been reported in association with NSAID treatment.

Other reported undesirable effects: anorexia, hypersensitivity phenomena such as skin rashes, headache, dizziness, drowsiness, malaise, tinnitus, deafness, asthenia, changes in haematological parameters, decreased hemoglobin and hematocrit, anemia.

As with other substances with similar action, increases in azotemia have been observed in some patients which do not progress beyond a certain level with continued administration; they return to normal values once therapy is discontinued.

Allergic edema of the face and hands, increased skin photosensitivity, visual disturbances, aplastic anemia, haemolytic anemia, pancytopenia, thrombocytopenia, Schoenlein-Henoch purpura, eosinophilia, increased liver function indices, jaundice may occur rarely, with rare cases of fatal hepatitis.

Rare cases of pancreatitis have been reported. Some cases of haematuria, dysuria, acute renal failure, water retention, which can manifest itself in the form of edema especially in the sloping regions of the lower limbs or cardiocirculatory disorders (hypertension, decompensation) have been reported.

Cases of nephrotic syndrome, glomerulonephritis, interstitial nephritis, renal failure have been reported.

Sporadic cases have been reported: epistaxis, dry mouth, erythema multiforme, ecchymosis, skin peeling, sweating, hypoglycemia, hyperglycaemia, changes in body weight, erethism, insomnia, depression, bladder dysfunction, shock and warning symptoms, alopecia, disorders of the "Nail growth, bullous reactions. Serious cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.4).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at: www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose

Symptoms: The most indicative symptoms of overdose are headache, vomiting, drowsiness, dizziness and syncope.

In the event of an overdose, symptomatic supportive therapy is indicated.

Although no studies have been performed so far, hemodialysis is unlikely to be useful in facilitating the elimination of piroxicam, as the drug is characterized by high plasma protein binding.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs.

ATC code: M01AC01.

Piroxicam, belonging to the class of benzothiazine carboxiamides-N-heterocyclics, is the first compound of a new group of NSAIDs, the oxicams. Piroxicam has anti-inflammatory, analgesic and antipyretic activity, pharmacological actions similar to those of other non-steroidal anti-inflammatory drugs. Animal studies have shown that piroxicam affects cell migration to sites of inflammation. Like other NSAIDs, piroxicam interferes with prostaglandin synthesis by inhibiting cyclooxygenase. Unlike indomethacin, piroxicam is a reversible inhibitor of prostaglandin synthesis. In a study of 9 patients with active rheumatoid arthritis, piroxicam (20 mg / day for 15 days) was shown to markedly lower the function of polymorphonuclear cells (PMN), the production of superoxide anions in peripheral blood and synovial fluid and the concentration of PMN and PMN elastase in the synovial fluid. The modulation of PMN responses may contribute to the anti-inflammatory action of piroxicam.

05.2 Pharmacokinetic properties

Absorption and distribution

Piroxicam is readily absorbed after oral administration. After oral administration, the presence of food reduces the rate, but not the percentage of active ingredient absorbed.

With a single administration the concentration is stable throughout the day.

Continuous treatment with 20 mg / day for periods of 1 year produces blood levels similar to those found after the first attainment of steady state.

Plasma drug concentrations are proportional for the 10 mg and 20 mg doses and generally peak within 3-5 hours of administration.Peak plasma levels of piroxicam of 1.5 to 2 mcg / ml are generally achieved with a single 20 mg dose, while after repeated daily doses of 20 mg of piroxicam, peak plasma concentrations of the drug usually stabilize at levels 3 to 8 mcg / ml. Most patients achieve plasma levels of steady state within 7-12 days.

A dosing regimen with loading doses of 40 mg / day for the first two days, followed subsequently by doses of 20 mg / day, allows for the attainment of the steady state immediately after the second dosage in a high percentage of cases (about 76%). Levelssteady state, the area under the curve and the elimination half-life are similar to those achieved with a regimen of 20 mg / day.

A multiple-dose comparative study of the pharmacokinetics and bioavailability of piroxicam sublingual tablets versus piroxicam oral capsules demonstrated that, after once daily dosing for 14 days, the time to reach mean plasma concentrations of piroxicam for capsules and sublingual tablets it was almost overlapping. There were no significant differences between the values steady state mean of Cmax, Cmin, T½ and Tmax. The study therefore highlights the bioequivalence of piroxicam sublingual tablets with the capsules, after once daily administration. Single dose studies have also demonstrated bioequivalence, both when taking the tablets with water and without water.

Metabolism and elimination

Piroxicam is largely metabolised in the body, and less than 5% of the daily dose is excreted unchanged in faeces and urine. The metabolism of piroxicam is predominantly mediated in the liver via the cytochrome P450 isoenzyme CYP 2C9. An important metabolic pathway is the hydroxylation of the pyridine ring of the side chain, followed by conjugation with glucuronic acid and elimination via the urine. The plasma half-life in humans is approximately 50 hours.

Patients with known or suspected decreased metabolic activity for CYP2C9 based on history / previous experience with other CYP2C9 substrates should be administered with caution, as they may have excessively high plasma concentrations due to decreased metabolic clearance (see section 4.4). .

Pharmacogenetics

CYP2C9 activity is reduced in individuals with genetic polymorphisms, such as CYP2C9 * 2 and CYP2C9 * 3 polymorphisms. Limited data from two published reports showed that subjects with CYP2C9 * 1 / * 2 heterozygous genotypes (n = 9), heterozygous CYP2C9 * 1 / * 3 (n = 9) and homozygous CYP2C9 * 3 / * 3 (n = 1) showed systemic levels of piroxicam 1.7, 1.7 and 5 times higher, respectively, than in subjects with the genotype CYP2C9 * 1 / * 1 (n = 17, genotype of normal metabolizer) after administration of a single oral dose. The elimination half-life values of piroxicam for subjects with CYP2C9 * 1 / * 3 genotypes (n = 9) and CYP2C9 * 3 / * 3 (n = 1) were 1.7 and 8.8 times higher than those of CYP2C9 * 1 / * 1 genotype subjects (n = 17). The frequency of the homozygous * 3 / * 3 genotype is estimated to range from 0% to 5.7% in various ethnic groups (see section 4.4).

05.3 Preclinical safety data

Non-clinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.

As with other substances that inhibit prostaglandin synthesis, piroxicam also increases the incidence of dystocia and post-term births in animals when the drug continues during pregnancy. The administration of NSAIDs to pregnant rats can cause constriction. of the fetal ductus arteriosus. Furthermore, in the last trimester of pregnancy, gastroduodenal toxicity increases.

In non-clinical studies, some effects such as gastrointestinal lesions and renal papillary necrosis were observed, detected at the maximum dose used, which is approximately 60 times greater than the indicated dose for humans.

This exposure to piroxicam is therefore considered to be sufficiently in excess of the maximum exposure in humans, indicating little relevance of these effects for the clinical use of the drug.

There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).